Texaphyrin-phospholipid conjugates and methods of preparing same

Patent metadata

Field	Value
Publication number	US-2018104364-A1
Application number	US-201615567294-A
Country	US
Kind code	A1
Filing date	Apr 14, 2016
Priority date	Apr 17, 2015
Publication date	Apr 19, 2018
Grant date	—

Abstract

There is provided herein, a texaphyrin-phospholipid conjugate, wherein the texaphyrin-phospholipid conjugate comprises a texaphyrin, texaphyrin derivative or texaphyrin analog covalently attached to a lipid side chain of a phospholipid.

First claim

1 . A texaphyrin-phospholipid conjugate, wherein the texaphyrin-phospholipid conjugate comprises a texaphyrin, texaphyrin derivative or texaphyrin analog covalently attached to a lipid side chain of a phospholipid.

2 . The conjugate of claim 1 , wherein the texaphyrin, texaphyrin derivative or texaphyrin analog is attached to the lipid side chain at the sn-1 or the sn-2 position.

3 . The conjugate of claim 16 wherein the texaphyrin, texaphyrin derivative or texaphyrin analog is texaphyrin.

4 . The conjugate of claim 1 wherein the phospholipid in the porphyrin-phospholipid conjugate comprises phosphatidylcholine, phosphatidylethanoloamine, phosphatidylserine or phosphatidylinositol.

5 . The conjugate of claim 4 , wherein the phospholipid comprises an acyl side chain of 12 to 22 carbons.

6 . The conjugate of claim 1 wherein the texaphyrin, texaphyrin derivative or texaphyrin analog is conjugated to the glycerol group on the phospholipid by a carbon chain linker of 0 to 20 carbons.

7 . The conjugate of claim 1 , complexed with a metal, selected from Mn, Fe, Co, Zn, Y, Cd, In, La, Hg, Pb, Bi, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu.

8 . A nanoparticle comprising the texaphyrin-phospholipid conjugate of claim 1 .

9 . The nanoparticle of claim 8 comprising at least 15, 25, 35, 45, 55, 65, 75, 85, 95 or 100 molar % texaphyrin-phospholipid conjugate.

10 . The nanoparticle of claim 8 further comprising a pegylated material selected from PEG, PEG-lipid, and PEG-DSPE.

11 - 12 . (canceled)

13 . The nanoparticle of claim 10 wherein the pegylated material is present in an amount of about 5 molar %.

14 . (canceled)

15 . The nanoparticle of claim 8 , being a bilayered vesicle or a monolayered vesicle.

16 . (canceled)

17 . The nanoparticle of claim 8 , wherein the nanoparticle is substantially spherical and between about 3 nm and about 200 nm in diameter.

18 . (canceled)

19 . The nanoparticle of claim 8 , further comprising an active agent encapsulated therein.

20 . The nanoparticle of claim 8 , further comprising targeting molecule.

21 . A method of preparing the texaphyrin-phospholipid conjugate of claim 1 , comprising reacting

with

to yield

under suitable reaction conditions;
wherein any of compounds 6 and 7 can be optionally substituted as necessary to yield a compound 8 comprising a desired texaphyrin, texaphyrin derivative or texaphyrin analog; and the phospholipid in compounds 6 and 8 may be replaced with any suitable phospholipid.

22 . The method of claim 21 , wherein

is prepared by reducing:

under suitable reaction conditions;
wherein any of compounds 5 and 6 can be optionally substituted as necessary to yield compound 8 comprising a desired texaphyrin, texaphyrin derivative or texaphyrin analog;
and the phospholipid in compounds 5 and 6 may be replaced with any suitable phospholipid.

23 . The method of claim 22 , wherein

is prepared by reacting

under suitable reaction conditions;
wherein compound 4 can be optionally substituted as necessary to yield compound 8 comprising a desired texaphyrin, texaphyrin derivative or texaphyrin analog;

and

may be replaced as desired with any suitable phospholipid.

24 - 25 . (canceled)

26 . The method of claim 21 , further comprising synthesizing a texaphyrin, texaphyrin derivative or texaphyrin analog, comprising cleaving the texaphyrin, texaphyrin derivative or texaphyrin analog from the conjugate.

27 . (canceled)

28 . The method of claim 26 , wherein the cleaving is performed using an enzyme, preferably a cleaving enzyme.

29 - 30 . (canceled)

Assignees

• Univ Health Network

Inventors

• Zheng Gang
• Keca Joseph

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07F9/106

  Adducts, complexes, salts of phosphatides · CPC title

• C07D487/22

  in which the condensed system contains four or more hetero rings · CPC title

• C12P17/182

  Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system (alloxazine or isoalloxazine, e.g. riboflavine C12P25/00) · CPC title